Psoriasis vulgaris (MIM 177900) is a skin disease characterized by inflammatory cell infiltration and hyperproliferation of epidermal cells.
A genetic factor is thought to be deeply involved in the onset of this disease. Investigation into the existing region of the causative gene responsible for the disease is in progress. For example, the sequence of a DNA of 2,229,817 bp, predicted to contain a sensitive gene of psoriasis, has been determined (The MHC sequencing consortium, Nature 400:921-923, 1999). The present inventors narrowed the scope of the existing region of the causative gene of psoriasis vulgaris by microsatellite analyses (Oka et al., Hum. Mol. Genet. 8:2165-2170, 1999) and found three known genes from the genomic sequence of HLA class I [i.e., POU5F1 (OTF3: octamer transcription factor 3), TCF19 (SC1: cell growth regulated gene), and MHC S]; as well as four novel genes within the region [i.e., HCR (helix coiled-coil rod homologue), SPR1 (skin specific proline rich gene 1), SEEK1 (specific expressed gene in epidermal keratinocytes 1), and STG (skin specific telomeric gene) (AB029331, AB031480, AB031479, and AB031481, respectively)] (Oka et al., Hum. Mol. Genet. 8:2165-2170, 1999) (FIG. 1).
Psoriasis vulgaris is known to show a strong positive association with HLA-Cw6/7 among these genes (Tiilikainen et al., Br. J. Dermatol., 102, 179-184, 1980; Bhalerao et al., Hum. Mol. Genet. 7:1537-1545, 1998). However, it remains to be seen whether the HLA genes themselves are responsible for the onset of psoriasis or whether some other non-HLA genes linked to the HLA genes are responsible.
Recently, a significant association between psoriasis and dimorphisms (Ser410Leu substitution) at cDNA position +1243 of the MHC S gene (the product of which are also called “corneodesmosin”) were reported in Caucasian populations (Tazi-Ahnini et al., Hum. Mol. Genet. 8:1135-1140, 1999; Allen et al., The Lancet 353:1589-1590, 1999). However, according to these papers, Tazi-Ahnini et al. reported a significant increase of the allele of Leu at position +1243, while Allen et al. reported an increase of another allele (Ser). Thus, the accuracy of these reports has been questioned.
The present inventors previously observed that psoriasis in a Japanese population was significantly associated with HLA-Cw6/7, as in the case of Caucasian (Ozawa et al., J. Am. Acad. Dermatol. 4:205-230, 1981; Asahina et al., J. Invest. Dermatol. 97:254-258, 1991); however, they also reported that no genetic polymorphism of the MHC S gene, significantly associated with psoriasis vulgaris, could be found (Ishihara et al., Tissue Antigens 48:182-186, 1996).
Thus, genes responsible for psoriasis vulgaris have not yet been identified. Additionally, only few reports on genetic polymorphisms that may be used as the target of testing for psoriasis vulgaris have been published.